title: CRF type 2 receptors mediate the metabolic effects of ghrelin in C2C12 cells.
abstract: OBJECTIVE
  Ghrelin is known to regulate appetite control and cellular metabolism. The corticotropin-releasing factor (CRF) family is also known to regulate energy balance. In this study, the links between ghrelin and the CRF family in C2C12 cells, a mouse myoblast cell line was investigated.
  
  
  METHODS
  C2C12 cells were treated with ghrelin in the presence or absence of CRF receptor antagonists and then subjected to different metabolic analyses.
  
  
  RESULTS
  Ghrelin enhanced glucose uptake by C2C12 cells, induced GLUT4 translocation to the cell surface and decreased RBP4 expression. A CRF-R2 selective antagonist, anti-sauvagine-30, blocked ghrelin-induced glucose uptake, Ghrelin upregulated CRF-R2 but not CRF-R1 levels. Moreover, ghrelin-treated C2C12 cells displayed a cAMP and pERK activation in response to Ucn3, a CRF-R2 specific ligand, but not in response to CRF or stressin, CRF-R1 specific ligands. Ghrelin also induced UCP2 and UCP3 expression, which were blocked by anti- sauvagine-30. Ghrelin did not induce fatty acids uptake by C2C12 cells or ACC expression. Even though C2C12 cells clearly exhibited responses to ghrelin, the known ghrelin receptor, GHSR1a, was not detectable in C2C12 cells.
  
  
  CONCLUSIONS
  The results suggest that, ghrelin plays a role in regulating muscle glucose and, raise the possibility that suppression of the CRF-R2 pathway might provide benefits in high ghrelin states.
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, North Torrey Pines Road, La Jolla, California, 10010, USA.
authors.forename: Eran
authors.initials: E
authors.lastname: Gershon
authors.forename: Wylie W
authors.initials: WW
authors.lastname: Vale
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007473:Ion Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D054839:Retinol-Binding Proteins, Plasma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D054832:Urocortins / Q000378:metabolism; D000099052:CRF Receptor, Type 1
chemical_list: D019138:Antibodies, Blocking; D054439:Ghrelin; D005947:Glucose; D051275:Glucose Transporter Type 4; D007473:Ion Channels; D024101:Mitochondrial Proteins; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D054440:Receptors, Ghrelin; D054839:Retinol-Binding Proteins, Plasma; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D054832:Urocortins; D000099052:CRF Receptor, Type 1; C101531:CRF receptor type 2; C000592182:Ghsr protein, Mouse; C502487:Rbp4 protein, mouse; C495693:Slc2a4 protein, mouse; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; C103016:antalarmin; C549823:urocortin 3 protein, mouse